Kidney failure can cause accumulation in body fluids, such as blood, of toxins and derivatives and metabolites of organic drugs taken by the patient. Sorbent dialysis systems provide treatment for patients with acute or chronic kidney disease. Dialysate is delivered to a dialyzer in prescribed amounts to cleanse the blood of impurities, correct the patient's body chemistry, and remove excess fluid. In sorbent dialysis, a sorbent cartridge can purify the initial dialysate and continuously regenerate spent dialysate throughout the treatment. Closed loop multi-pass sorbent based dialysis systems, for example, regenerate dialysate for reuse by passing spent dialysate through a regeneration section comprising a plurality of sorbent cartridges and suitable additives. Spent dialysate comprising urea, which is diffused from impure blood in the dialyzer, passes through sorbent cartridges. The sorbent cartridges bind uremic wastes, and also can be used for other tasks, such as balancing dialysate pH. A typical sorbent cartridge system comprises, for example, an enzyme layer consisting of urease, a cation exchange layer consisting of zirconium phosphate, an anion exchange layer consisting of hydrous zirconium oxide (HZO), and an adsorbent layer consisting of activated carbon. The REDY™ (REgenerative DialYsis) System is an example of a commercially available sorbent cartridge system which uses a similar arrangement of sorbents. During regenerative dialysis, the used or spent dialysate moves up through the layers of the cartridge. The enzymatic urease converts urea into ammonium carbonate. The ammonia and ammonium ions are then removed by the zirconium phosphate in exchange for H+ and Na+ ions. The carbonate from the urea hydrolysis then combines with H+ to form bicarbonate (HCO3−) and carbonic acid (H2CO3). Carbonic acid is an unstable organic acid; most of it rapidly breaks down into water and carbon dioxide molecules (CO2). The HZO (e.g., containing acetate as a counter ion) removes HCO3−, P−, and other anions (e.g., F− in water), and releases acetate. The activated carbon absorbs organic metabolites such as creatine, uric acid, and nitrogenous metabolic waste of the patient as well as chlorine and chloramines from the water. The CO2 gas bubbles are vented from the cartridge.
The present investigators have recognized that conventional sorbent dialysis can be inadequate to remove uremic toxins which include anions, organic solutes, or both. The present investigators further have recognized that HZO used as a clinical sorbent for some sorbent dialysis to remove phosphate from patients with renal diseases has limited adsorption capacity for uremic toxins such as sulfate and other toxic anions as well as organic solutes in spent dialysate, especially in the presence of phosphate.